Essential Tremor (ET), a condition characterized by postural and kinetic tremor in the upper limbs, is one of the most prevalent movement disorders. While pharmaceutical and surgical treatment options exist, they are not ideal. Assistive devices have the potential to provide relief to patients but are largely unexplored for ET. Furthermore, prior characterizations of essential tremor have focused on endpoint tremor and provide insufficient detail for designing such a device. We propose and demonstrate a novel method for characterizing essential tremor in the 7 proximal degrees of freedom (DOF) of the upper limb in various postures. In addition, we provide a preliminary characterization in a small number of patients with mild ET. We collected data from 10 patients with ET. Subjects were instrumented with four electromagnetic sensors that recorded orientation of upper limb segments. After a calibration, each subject positioned his/her upper limb in 16 different postures for 15 seconds each. This procedure was repeated 4 times for each subject, with each repetition being considered a run. Sensor data were converted to angular kinematic data for each DOF using inverse kinematics, a practice unique to this study. These data were then analyzed in the frequency domain to calculate the power associated with the tremor in each DOF and posture. More specifically, we computed the area of the periodogram over the 4-12 Hz frequency band typically associated with ET [narrow-band area (NBA)] and over the wider frequency band from 2 Hz to the Nyquist frequency [wide-band area (WBA)]. If significant peaks were found in the 4-12 Hz band, their frequency and amplitude were reported. Mixed-model ANOVA tests were used to investigate effects of DOF, posture, run, gravity, and patient characteristics on reported measures. NBA and WBA varied significantly between DOF, being lowest in the wrist, intermediate in the shoulder, and greatest in the elbow and forearm (pronation-supination). NBA and WBA also varied significantly with posture. Only 5% of observations had significant peaks, with 49% of peaks occurring in wrist flexion-extension and 39% occurring in wrist radial-ulnar deviation. Peak frequency was quite stereotyped (5.7 Hz ± 1.3Hz). Run had no significant effects, indicating that tremor measures were consistent over the duration of the experiment. Effects of gravity and demographic factors on measures were mixed and did not present a discernible pattern. This preliminary characterization suggests that tremor may be focused in a subset of upper limb DOF, being greatest (in terms of power) in elbow flexion-extension and forearm pronation-supination, and most concentrated (with peaks at a stereotyped frequency) in wrist flexion-extension and radial-ulnar deviation. Our method of 7 DOF characterization through inverse kinematics, in conjunction with future research (isolation studies, EMG, and finger DOF) may allow for optimal tremor suppression by an orthosis.

No description available.

Optimized peripheral tremor suppression could address many limitations of surgical or medicinal treatments of Essential Tremor, however it is not well understood how the tremorogenic activity is distributed among the muscles of the upper limb, and therefore how to optimize such suppression. We recorded electromyographic (EMG) activity in the 15 major superficial muscles from the shoulder to the wrist while subjects performed postural and kinetic tasks similar to activities of daily living. We calculated the power spectral density and computed the total power in the tremor band (4"12 Hz) for each muscle, from which we determined the distribution of tremorogenic activity among the 15 muscles for various conditions. Differences in distribution between conditions were quantified as Pearson correlation coefficients. All 15 muscles exhibited some tremorogenic activity. The anterior deltoid exhibited by far the most power, the wrist extensors had more power than other distal muscles, and the triceps longus showed the least power. Distributions among muscles was highly consistent across repetitions (r = 0.91 ± 0.07) and somewhat stereotyped across subjects (r = 0.58 ± 0.31). Differences in task (postural vs. kinetic), limb configuration, and subject characteristics (sex; tremor severity, onset, and duration) had little effect on distribution (r =0.84). Interestingly, the distribution of tremorogenic activity was highly correlated (r = 0.94 ± 0.08) with the distribution of voluntary activity (power between 0.5 and 4 Hz). In particular, muscles opposing gravity had the highest amount of tremorogenic activity. This may explain in part why the distribution of tremorogenic activity was stereotyped across subjects.

Essential tremor (ET) is the most common movement disorder worldwide and is characterized by an isolated tremor of the upper limb that worsens over the course of time. Evidence has accumulated to support the theory that the cerebellum is primary involved in the development of ET disease, although the contribution of cerebellar pathology to ET’s aetiology remains poorly understood. Beside motor deficits, numerous studies report the presence of cognitive impairment in ET patients. The cerebellum is crucial for motor as well as cognitive functions as it integrates sensorimotor information to create an internal model of movement using prediction errors. In this study, I tested the performance of 34 ET patients and 34 age-matched healthy controls in a visuomotor adaptation (VMA) task whose proper execution critically depends on the cerebellum. Participants performed the VMA while sitting in front of a computer screen. At the beginning of each trial, eight grey circles in one of eight possible positions arrayed around a central cross appeared on the screen. Next, one of the eight circles was marked as a blue target, and participants had to move from the central cross towards the target using a digital pen moved on a digital tablet. The movement on the tablet was represented as a cursor on the screen. Visual feedback from the moving hand was prevented. Over the course of the experiment, a 30° clockwise visuomotor perturbation of the cursor movement on the screen was introduced abruptly. To this end, subjects implicitly modified the reach direction such that they are able to hit the target again. The extent to which a subject adapts to the visuomotor perturbation can be measured by the angular error between a straight line connecting the center cross and the target, and a line connecting the center cross and the position of the cursor at peak velocity. Reaction times and movement times were analyzed to assess motor performance. In accordance with my hypothesis, I found evidence for impaired visuomotor adaptation in ET that could not be explained by altered general motor performance due to tremor. This deficit was also specific to both early and late adaptation phases. There were no group differences during a baseline phase, in which no visual perturbation was present, as well as at a de-adaptation phase, when the visual perturbation was suddenly removed. This deficit seems to also not relate to clinical features, i.e., disease state (measured by TETRAS/SARA), disease duration, current medication, and patients’ cognitive state (evaluated by MoCA). Thus, these findings support the hypothesis that a functional disturbance of the cerebellum is present in mildly to moderately affected ET patients without marked cerebellar signs and is detectable using a behavioral task that targets cerebellar functionality. What could be further mechanisms that negatively affect visuomotor adaptation in patients with ET and are not associated with basic motor functions? Unlike a pure motor task, the visuomotor adaptation task entails a cognitive component with implicit and/or explicit learning processes. Thus, it could be that cognitive deficits in ET, frequently reported among studies may have driven performance deficits in this task. Note however that I did not find any association between cognitive abilities as measured by MoCA and visuomotor adaptation impairment in the ET cohort. As no extensive neurocognitive testing was performed in our cohort and MoCA was shown to be not very sensitive for cerebellar cognitive symptoms, it is impossible to rule out the effect of cognitive decline in ET on visuomotor adaptation.

This study seeks to understand upper limb tremor in subjects with essential tremor (ET). A thorough understanding of tremor distribution will allow for the more effective development of tremor suppression devices, which offer an alternative to current treatments. Previous studies primarily focused on tremor in the hand only. This study seeks to characterize the distribution of tremor throughout the upper limb. We measured tremor in 25 subjects diagnosed with ET using motion capture, which provided 0displacement information of the limb during multiple postural and kinetic tasks. Inverse kinematics allowed us to analyze the motion capture data in the 7 major degrees of freedom (DOF) of the upper limb. The power spectral density estimate was used to determine: relative tremor magnitude throughout the DOFs, tremor variation between tasks, variation between subjects, and frequency variations between DOFs. Data analysis revealed that tremor increase is roughly proximal to distal. We also show that tremor magnitude in kinetic tasks is significantly higher than in postural tasks. Although we found some variation in tremor distribution between subjects, the roughly proximal to distal increase in tremor severity holds for several subsets of the study population. Finally, we found that tremor frequency doesnt vary significantly (<<> 1 Hz) between DOFs, in subjects with severe tremor. Our study shows that tremor distribution is quite stereotyped between subjects with ET. Furthermore, we have shown that tremor is greatest in the distal DOFs. This provides a compelling starting point for the development of future tremor suppression devices.

Accurate Detection of Parkinson`s Disease in Tremor Syndromes Using Olfactory Testing

Ces travaux de thèse portent sur l'étude de nouvelles modalités de guidage de la thérapie transcrânienne par ultrasons focalisés, technique non invasive particulièrement prometteuse pour le traitement de troubles neurologiques tels que le tremblement essentiel ou le tremblement parkinsonien. Une nouvelle technique d'imagerie par résonance magnétique a tout d'abord été utilisée pour imager l'emplacement du faisceau ultrasonore produit par un prototype préclinique : les déplacements induits par les ultrasons dans une cervelle de veau ex vivo ont été imagés sans distorsion à l'aide d'une séquence d'écho de spin accélérée, avec un dépôt d'énergie jusqu'à quatre fois inférieur aux techniques existantes. Nous avons ensuite étudié les effets directs des ultrasons sur l'activité cérébrale par neuromodulation ultrasonore in vivo, de façon similaire à la stimulation magnétique transcrânienne, mais avec les capacités de ciblage millimétriques des ultrasons focalisés. Des expériences ont été tout d'abord menées sur un modèle de rat anesthésié afin d'étudier la pression seuil pouvant induire un effet moteur. Le champ acoustique simulé dans la tête de rat est fortement affectée par des réverbérations, ce qui doit être pris en compte pour l'évaluation in situ des paramètres acoustiques de neurostimulation, en particulier à basse fréquence et pour les petits animaux. Enfin, pour la première fois, nous avons montré que les ultrasons focalisés de faible intensité pouvaient moduler de façon causale le comportement d'un primate non humain éveillé : le temps de latence d'une tâche d'anti-saccade est retardé de façon significative par des ultrasons focalisés dans le champ visuel frontal. / The work presented in this thesis investigates novel modalities to guide Transcranial Magnetic Resonance guided Focused Ultrasound (TcMRgFUS). TcMRgFUS is an emerging and promising non-invasive technique for the treatment of neurological disorders, such as essential tremor or Parkinsonian tremor. A novel Magnetic Resonance Acoustic Radiation Force Imaging (MRARFI) has been used to image the location of the ultrasonic beam produced by a preclinical prototype: an accelerated 2D spin-echo MR ARFI pulse sequence has been introduced to generate undistorted ultrasound-induced displacement maps in ex vivo veal brains with minimum energy deposition. We then investigated direct effects of the ultrasonic beam on brain activity by conducting in vivo ultrasonic neuromodulation, similarly to what is currently achieved with transcranial magnetic stimulation (TMS) but with the millimetric targeting capabilities of the ultrasound. Experiments have been first conducted in an anesthetized rat model to investigate the motor threshold. Numerical simulations have shown that the acoustic pattern in the rat head is affected by reverberations and that special care must be taken when relating acoustic parameters to neurostimulation effects, especially at a low frequency and for small animals. Finally, for the first time, we used low intensity FUS stimulation to causally modulate behavior in an awake nonhuman primate brain. We showed that the latency of an anti-saccade task was delayed significantly in the presence of ultrasonic beam focused in the Frontal Eye Field. Sham experiments did not show any significant change in the latencies.

Background: The posterior subthalamic area (PSA) is essentially composed of the caudal Zona incerta and the prelemniscal radiation. Subthalamotomy in the PSA was renowned for its effectiveness in alleviating movement disorders and particularly tremor. The modern literature on DBS of this area is limited, but promising results have been presented for Parkinson’s disease (PD), essential tremor (ET) and other movement disorders.   Aim: To evaluate the safety of PSA DBS with emphasis on the panorama of side effects, the distribution of stimulation-induced side effects and the effects of PSA DBS on verbal fluency. To evaluate the therapeutic effect of PSA DBS on less common forms of tremor, tremor-dominant PD, and concerning the long-term results in ET. Method: 40 patients were evaluated regarding side effects of the procedure. 28 patients with ET were analyzed for stimulation-induced side effects in a standardized manner. The locations of the contacts that caused stimulation-induced side effects were plotted on atlas slides. A 3-D model of the area was created based on these slides. Verbal fluency was analyzed in 17 patients with ET before surgery, after 3 days and finally after 1 year. Five patients with less common forms of tremor and 18 with ET were evaluated according to the ETRS at baseline and one year or 3-5 years after surgery, respectively. 14 patients with mainly unilateral tremor-dominant PD were evaluated a mean of 18 months after surgery according to the motor part of UPDRS. Results: PSA DBS was associated with few serious side-effects, but a transient and mild postoperative dysphasia was found in 22.5% of the patients. There was a slight transient decline in the performance on verbal fluency tests immediately after surgery. Visualization of the contacts causing stimulation-induced side effects showed that identical responses can be elicited from various points in the PSA and its vicinity. The effect on the less common forms of tremor was excellent except for neuropathic tremor where the effect was moderate. A pronounced and sustained microlesional effect was seen for some of the patients. After a mean of 4 years with unilateral PSA DBS the total ETRS score was improved by 52.4%, tremor by 91.8% and hand function by 78.0% in the patients with ET. There was no increase in the stimulation strength over time. In PD, the scores improved 47.7% for contralateral UPDRS III. Contralateral tremor, rigidity, and bradykinesia improved by 82.2%, 34.3%, and 26.7%, respectively. Conclusions: PSA DBS generally seem to be a safe procedure, but it may be associated with transient declines of verbal fluency. There was no clear somatotopic pattern with regard to stimulation-induced side effects in the PSA. PSA DBS can alleviate tremor regardless of the etiology. The long-term effects in ET were favorable when compared to our previous results of Vim DBS. The effect on Parkinsonian tremor was satisfying, however, the reductions of rigidity and bradykinesia were less compared to previous studies of PSA DBS for PD.

Essential voice tremor (EVT) is a voice disorder that results from dyscoordination within the laryngeal musculature, which negatively impacts the symmetrical motion of the vocal folds. Several investigators have shown that individuals with EVT experience difficulty speaking and a reduced quality of life (QOL; Cohen, Dupont, & Courey, 2006; Verdonck-de Leeuw & Mahieu, 2004). While traditional voice therapy has been ineffective in lessening the severity of vocal tremor, a current approach (Barkmeier- Kraemer, Lato, & Wiley, 2011) designed to lessen the perception of vocal tremor has resulted in reported patient satisfaction with little actual change in voice quality. The present study focused on achieving positive voice changes by targeting the physiological aspects of voice production that may be altered through inspiratory breathing techniques, i.e., increased lung volume pressure and laryngeal lowering. The hypothesis was that such changes could result in reductions in vocal tremor and lead to perceived improvements in voice quality and concomitant increases in the participant's QOL. An ABAB (treatment reversal) single subject design was used to assess the effectiveness of inspiratory breathing exercises on reducing the severity of tremor in three women diagnosed with EVT. Pre-treatment measures were administered, and participant progress was determined after one week of treatment (post-treatment #1), a week of no treatment, and another week of treatment (post-treatment #2). The following measures were gathered from each participant to document treatment progress and effectiveness:lung pressure volume levels, Voice Handicap Index (VHI) ratings, acoustic analyses of isolated vowels, and perceptual ratings on the Consensus Auditory Perceptual Evaluation of Voice (CAPE-V), as well as untrained listener ratings of vocal steadiness and pleasantness. Physiological, QOL, acoustic, and perceptual data did not triangulate to demonstrate treatment effectiveness. However, individual treatment effects were found in increases in lung pressure volume for participant 1, decreases in CAPE-V scores for participant 3, and decreases in VHI scores for participants 1 and 3. Changes in voice acoustics and untrained listener perceptions were negligible. Thus, the results from this study indicate that inspiratory breathing exercises may show some promise in improving voice and QOL in certain tremor patients and that this technique warrants further research consideration.

Objective: To determine the effects of head position and of different postural control demands on head tremor measures in participants with essential tremor. Methods: Seventeen participants with essential tremor (ET) of the head and 17 control participants took part. Individuals held their heads in varying degrees of rotation, flexion, and extension. Subsequently, individuals sat and stood in different postures, incorporating different foot placements (feet apart and together), surfaces (solid and foam), and vision conditions (eyes open and closed). Neck muscle activity was recorded from three muscles bilaterally (trapezius, sternocleidomastoid, splenius capitis). Three-dimensional head and thorax positions were recorded using an Optotrak system, and head angular velocity with respect to thorax was calculated by differentiating tilt-twist angles. Fourier analysis was used to determine tremor power. Results: ET participants showed sharp peaks at their tremor frequency in spectral plots of kinematic data, whereas CN participants did not. Electromyography data was too noisy for frequency analysis. ET participants displayed increased tremor power in head positions 25° from neutral compared to neutral and positions 50° from neutral. Tremor power increased with increasing difficulty of posture for both participant groups. Removal of vision resulted in decreased tremor power in ET participants; power was significantly decreased in the easier postures, and progressively less so with increasing difficulty of posture. Interestingly, tremor direction was inconsistent in both groups, and two ET participants displayed multiple tremor peaks. Conclusions: The tilt-twist method is a feasible way of measuring head kinematics. Changing stiffness of the neck likely mediates the effect of head position on head tremor power, with the resultant interplay of the central driver and the mechanical resonance driving the amplitude changes. Decreasing stability of posture increases head tremor, likely due to the associated increase in postural sway and stress on the postural control system. Vision appears to exacerbate head tremor through the addition of tremor-related visual noise and an implicit task to stabilize vision; this is possible evidence of a visuomotor deficit. However, stabilizing vision becomes less important with increasing difficulty of posture, resulting in a narrowing gap in tremor power between vision and no vision conditions. / Thesis (Master, Rehabilitation Science) -- Queen's University, 2011-03-31 18:16:59.927